tbuckley/cabot-search huggingface dataset:
Preparedness of Eastern Mediterranean countries in view of monkeypox emergence during the COVID-19 pandemic: A call for action
Authors: Ramadan Abdelmoez Farahat, Tungki Pratama Umar, Sheharyar Hassan Khan, Abhigan Babu Shrestha, Ateeba Kamran, Mohammad Yasir Essar, Rehab H. El-Sokkary
Journal: International Journal of Surgery (2022)
A Novel Selective Inhibitor JBI-589 Targets PAD4-Mediated Neutrophil Migration to Suppress Tumor Progression
Authors: Hui Deng, Cindy Lin, Laura Garcia-Gerique, Shuyu Fu, Zachary Cruz, Erin E. Bonner, Matthew Rosenwasser, Sridharan Rajagopal, M Naveen Sadhu, Chandru Gajendran, Mohd Zainuddin, Ramachandraiah Gosu, Dhanalakshmi Sivanandhan, Miriam A. Shelef, Brian Nam, Dan T. Vogl, Dmitry I. Gabrilovich, Yulia Nefedova
Journal: Cancer Research (2022)

Neutrophils are closely involved in the regulation of tumor progression and formation of premetastatic niches. However, the mechanisms of their involvement and therapeutic regulation of these processes remain elusive. Here, we report a critical role of neutrophil peptidylarginine deiminase 4 (PAD4) in neutrophil migration in cancer. In several transplantable and genetically engineered mouse models, tumor growth was accompanied by significantly elevated enzymatic activity of neutrophil PAD4. Targeted deletion of PAD4 in neutrophils markedly decreased the intratumoral abundance of neutrophils and led to delayed growth of primary tumors and dramatically reduced lung metastases. PAD4-mediated neutrophil accumulation by regulating the expression of the major chemokine receptor CXCR2. PAD4 expression and activity as well as CXCR2 expression were significantly upregulated in neutrophils from patients with lung and colon cancers compared with healthy donors, and PAD4 and CXCR2 expression were positively correlated in neutrophils from patients with cancer. In tumor-bearing mice, pharmacologic inhibition of PAD4 with the novel PAD4 isoform-selective small molecule inhibitor JBI-589 resulted in reduced CXCR2 expression and blocked neutrophil chemotaxis. In mouse tumor models, targeted deletion of PAD4 in neutrophils or pharmacologic inhibition of PAD4 with JBI-589 reduced both primary tumor growth and lung metastases and substantially enhanced the effect of immune checkpoint inhibitors. Taken together, these results suggest a therapeutic potential of targeting PAD4 in cancer.PAD4 regulates tumor progression by promoting neutrophil migration and can be targeted with a small molecule inhibitor to suppress tumor growth and metastasis and increase efficacy of immune checkpoint blockade therapy.
Validation of Amazon Halo Movement: a smartphone camera-based assessment of movement health
Authors: Michael Fanton, Yaar Harari, Matthew Giffhorn, Allie Lynott, Eli Alshan, Jonathan Mendley, Madeline Czerwiec, Rebecca Macaluso, Ianir Ideses, Eduard Oks, Arun Jayaraman
Journal: npj Digital Medicine (2022)

Movement health is understanding our body's ability to perform movements during activities of daily living such as lifting, reaching, and bending. The benefits of improved movement health have long been recognized and are wide-ranging from improving athletic performance to helping ease of performing simple tasks, but only recently has this concept been put into practice by clinicians and quantitatively studied by researchers. With digital health and movement monitoring becoming more ubiquitous in society, smartphone applications represent a promising avenue for quantifying, monitoring, and improving the movement health of an individual. In this paper, we validate Halo Movement, a movement health assessment which utilizes the front-facing camera of a smartphone and applies computer vision and machine learning algorithms to quantify movement health and its sub-criteria of mobility, stability, and posture through a sequence of five exercises/activities. On a diverse cohort of 150 participants of various ages, body types, and ability levels, we find moderate to strong statistically significant correlations between the Halo Movement assessment overall score, metrics from sensor-based 3D motion capture, and scores from a sequence of 13 standardized functional movement tests. Further, the smartphone assessment is able to differentiate regular healthy individuals from professional movement athletes (e.g., dancers, cheerleaders) and from movement impaired participants, with higher resolution than that of existing functional movement screening tools and thus may be more appropriate than the existing tests for quantifying functional movement in able-bodied individuals. These results support using Halo Movement's overall score as a valid assessment of movement health.
Publisher Correction: Viral manipulation of functionally distinct interneurons in mice, non-human primates and humans
Authors: Douglas Vormstein-Schneider, Jessica D. Lin, Kenneth A. Pelkey, Ramesh Chittajallu, Baolin Guo, Mario A. Arias-Garcia, Kathryn Allaway, Sofia Sakopoulos, Gates Schneider, Olivia Stevenson, Josselyn Vergara, Jitendra Sharma, Qiangge Zhang, Tom P. Franken, Jared Smith, Leena A. Ibrahim, Kevin J. Mastro, Ehsan Sabri, Shuhan Huang, Emilia Favuzzi, Timothy Burbridge, Qing Xu, Lihua Guo, Ian Vogel, Vanessa Sanchez, Giuseppe A. Saldi, Bram L. Gorissen, Xiaoqing Yuan, Kareem A. Zaghloul, Orrin Devinsky, Bernardo L. Sabatini, Renata Batista-Brito, John Reynolds, Guoping Feng, Zhanyan Fu, Chris J. McBain, Gord Fishell, Jordane Dimidschstein
Journal: Nature Neuroscience (2022)
Obesity in women with asthma: Baseline disadvantage plus greater small‐airway responsiveness
Authors: Arnaud Bourdin, Sébastien Bommart, Gregory Marin, Isabelle Vachier, Anne Sophie Gamez, Engi Ahmed, Carey M. Suehs, Nicolas Molinari
Journal: Allergy (2022)

Obesity is known to diminish lung volumes and worsen asthma. However, mechanistic understanding is lacking, especially as concerns small-airway responsiveness. The objective of this study was therefore to compare small-airway responsiveness, as represented by the change in expiratory:inspiratory mean lung density ratios (MLDe/i , as determined by computed tomography [CT]) throughout methacholine testing in obese versus non-obese women with asthma.Thoracic CT was performed during methacholine bronchoconstriction challenges to produce standardized response curves (SRC: response parameter versus ln[1 + % PD20], where PD20 is the cumulative methacholine dose) for 31 asthma patients (n = 18 non-obese and n = 13 obese patients). Mixed models evaluated obesity effects and interactions on SRCs while adjusting for age and bronchial morphology. Small airway responsiveness as represented by SRC slope was calculated for each third of the MLDe/i response and compared between groups.Obesity-associated effects observed during experimental bronchoconstriction included: (i) a significant baseline effect for forced expiratory volume in 1 second with lower values for the obese (73.11 ± 13.44) versus non-obese (82.19 ± 8.78; p = 0.002) groups prior to methacholine testing and (ii) significantly higher responsiveness in small airways as estimated via differences in MLDe/i slopes (group×ln(1 + % PD20 interaction; p = 0.023). The latter were pinpointed to higher slopes in the obese group at the beginning 2/3 of SRCs (p = 0.004 and p = 0.021). Significant obesity effects (p = 0.035 and p = 0.008) indicating lower forced vital capacity and greater % change in MLDe/I (respectively) throughout methacholine testing, were also observed.In addition to baseline differences, small-airway responsiveness (as represented by the change in MLDe/i ) during methacholine challenge is greater in obese women with asthma as compared to the non-obese.
Use of Clinical Outcome Assessments in New Drug Approvals by the US Food and Drug Administration Divisions of Neurology I and II
Authors: Yvette Schein, Holly Fernandez Lynch
Journal: JAMA Network Open (2022)

This cross-sectional study examines drug approvals by the US Food and Drug Administration (FDA) Divisions of Neurology I and II to understand the role of clinical outcome assessments in regulatory decisions, including whether and how potential shortcomings are addressed.
Application of Statistical Learning to Identify Omicron Mutations in SARS-CoV-2 Viral Genome Sequence Data From Populations in Africa and the United States
Authors: Lue Ping Zhao, Terry P. Lybrand, Peter Gilbert, Margaret Madeleine, Thomas H. Payne, Seth Cohen, Daniel E. Geraghty, Keith R. Jerome, Lawrence Corey
Journal: JAMA Network Open (2022)

With timely collection of SARS-CoV-2 viral genome sequences, it is important to apply efficient data analytics to detect emerging variants at the earliest time.
Correction to: Antithrombotic Therapy for Symptomatic Peripheral Arterial Disease: A Systematic Review and Network Meta-Analysis
Authors: Loes H. Willems, Dominique P. M. S. M. Maas, Kees Kramers, Michel M. P. J. Reijnen, Niels P. Riksen, Hugo Ten Cate, Rozemarijn J. van der Vijver-Coppen, Gert J. de Borst, Barend M. E. Mees, Clark J. Zeebregts, Gerjon Hannink, Michiel C. Warlé
Journal: Drugs (2022)
Multivariable Predictive Models to Identify the Optimal Biologic Therapy for Treatment of Patients With Psoriasis at the Individual Level
Authors: Mia-Louise Nielsen, Troels Christian Petersen, Julia-Tatjana Maul, Jashin J. Wu, Mads Kirchheiner Rasmussen, Trine Bertelsen, Kawa Khaled Ajgeiy, Lone Skov, Simon Francis Thomsen, Jacob P. Thyssen, Alexander Egeberg
Journal: JAMA Dermatology (2022)

Identifying the optimal long-term biologic therapy for patients with psoriasis is often done through trial and error.To identify the optimal biologic therapy for individual patients with psoriasis using predictive statistical and machine learning models.This population-based cohort study used data from Danish nationwide registries, primarily DERMBIO, and included adult patients treated for moderate-to-severe psoriasis with biologics. Data were processed and analyzed between spring 2021 and spring 2022.Patient clusters of clinical relevance were identified and their success rates estimated for each drug. Furthermore, predictive prognostic models to identify optimal biologic treatment at the individual level based on data from nationwide registries were evaluated.Assuming a success criterion of 3 years of sustained treatment, this study included 2034 patients with a total of 3452 treatment series. Most treatment series involved male patients (2147 [62.2%]) originating from Denmark (3190 [92.4%]), and 2414 (69.9%) had finished an education longer than primary school. The average ages were 24.9 years at psoriasis diagnosis and 45.5 years at initiation of biologic therapy. Gradient-boosted decision trees and logistic regression were able to predict a specific cytokine target (eg, interleukin-17 inhibition) associated with a successful treatment with accuracies of 63.6% and 59.2%, and top 2 accuracies of 95.9% and 93.9%. When predicting specific drugs resulting in success, gradient boost and logistic regression had accuracies of 48.5% and 44.4%, top 2 accuracies of 77.6% and 75.9%, and top 3 accuracies of 89.9% and 89.0%.Of the treatment prediction models used in this cohort study of patients with psoriasis, gradient-boosted decision trees performed significantly better than logistic regression when predicting specific biologic therapy (by drug as well as target) leading to a treatment duration of at least 3 years without discontinuation. Predicting the optimal biologic could benefit patients and clinicians by minimizing the number of failed treatment attempts.
Errors in Author Affiliations
Authors: Ole Köhler-Forsberg, Christopher Rohde, Søren Østergaard, Köhler-Forsberg Rohde, Søren Dinesen Østergaard
Journal: JAMA Psychiatry (2022)

Nils R. Winter, MSc; Ramona Leenings, MSc; Jan Ernsting, MSc; Kelvin Sarink, MSc; Lukas Fisch, MSc; Daniel Emden, MSc; Julian Blanke, BSc; Janik Goltermann, MSc; Nils Opel, MD; Carlotta Barkhau, MSc; Susanne Meinert, MSc; Katharina Dohm, PhD; Jonathan Repple, MD; Marco Mauritz, MSc; Marius Gruber, MSc; Elisabeth J. Leehr, PhD; Dominik Grotegerd, PhD; Ronny Redlich, PhD; Andreas Jansen, PhD; Igor Nenadic, MD; Markus M. Nöthen, MD; Andreas Forstner, MD; Marcella Rietschel, MD; Joachim Groß, PhD; Jochen Bauer, PhD; Walter Heindel, MD; Till Andlauer, PhD; Simon B. Eickhoff, MD; Tilo Kircher, MD; Udo Dannlowski, MD, PhD; Tim Hahn, PhD
A New View of Activating Mutations in Cancer
Authors: Ruth Nussinov, Chung-Jung Tsai, Hyunbum Jang
Journal: Cancer Research (2022)

Abstract A vast effort has been invested in the identification of driver mutations of cancer. However, recent studies and observations call into question whether the activating mutations or the signal strength are the major determinant of tumor development. The data argue that signal strength determines cell fate, not the mutation that initiated it. In addition to activating mutations, factors that can impact signaling strength include (i) homeostatic mechanisms that can block or enhance the signal, (ii) the types and locations of additional mutations, and (iii) the expression levels of specific isoforms of genes and regulators of proteins in the pathway. Because signal levels are largely decided by chromatin structure, they vary across cell types, states, and time windows. A strong activating mutation can be restricted by low expression, whereas a weaker mutation can be strengthened by high expression. Strong signals can be associated with cell proliferation, but too strong a signal may result in oncogene-induced senescence. Beyond cancer, moderate signal strength in embryonic neural cells may be associated with neurodevelopmental disorders, and moderate signals in aging may be associated with neurodegenerative diseases, like Alzheimer's disease. The challenge for improving patient outcomes therefore lies in determining signaling thresholds and predicting signal strength.
Epithelial cell‐expressed type <scp>II IL</scp>‐4 receptor mediates eosinophilic esophagitis
Authors: Shmulik Avlas, Guy Shani, Natalie Rhone, Michal Itan, Avishay Dolitzky, Inbal Hazut, Sharon Grisaru‐Tal, Yaara Gordon, Tetsuo Shoda, Adina Ballaban, Netali Morgenstern Ben‐Baruch, Mark Rochman, Yael Diesendruck, Limor Nahary, Almog Bitton, Zamir Halpern, Itai Benhar, Chen Varol, Marc E. Rothenberg, Ariel Munitz
Journal: Allergy (2022)

Eosinophilic esophagitis (EoE) is a chronic, food-driven allergic disease, characterized by eosinophil-rich inflammation in the esophagus. The histopathological and clinical features of EoE have been attributed to overproduction of the type 2 cytokines IL-4 and IL-13, which mediate profound alterations in the esophageal epithelium and neutralizing of their shared receptor component (IL-4Rα) with a human antibody drug (dupilumab) demonstrates clinical efficacy. Yet, the relative contribution of IL-4 and IL-13 and whether the type II IL-4 receptor (comprised of the IL-4Rα chain in association with IL-13Rα1) mediates this effect has not been determined.Experimental EoE was induced in WT, Il13ra1-/- , and Krt14Cre /Il13ra1fl/fl mice by skin-sensitized using 4-ethoxymethylene-2-phenyl-2-oxazolin (OXA) followed by intraesophageal challenges. Esophageal histopathology was determined histologically. RNA was extracted and sequenced for transcriptome analysis and compared with human EoE RNAseq data.Induction of experimental EoE in mice lacking Il13ra1 and in vivo IL-13 antibody-based neutralization experiments blocked antigen-induced esophageal epithelial and lamina propria thickening, basal cell proliferation, eosinophilia, and tissue remodeling. In vivo targeted deletion of Il13ra1 in esophageal epithelial cells rendered mice protected from experimental EoE. Single-cell RNA sequencing analysis of human EoE biopsies revealed predominant expression of IL-13Rα1 in epithelial cells and that EoE signature genes correlated with IL-13 expression compared with IL-4.We demonstrate a definitive role for IL-13 signaling via IL-13Rα1 in EoE. These data provide mechanistic insights into the mode of action of current therapies in EoE and highlight the type II IL-4R as a future therapeutic target.
Extracellular sulfatase-2 is overexpressed in rheumatoid arthritis and mediates the TNF-α-induced inflammatory activation of synovial fibroblasts
Authors: Ruby J. Siegel, Anil K. Singh, Paul M. Panipinto, Farheen S. Shaikh, Judy Vinh, Sang U. Han, H. Mark Kenney, Edward M. Schwarz, Cynthia S. Crowson, Sadik A. Khuder, Basil S. Khuder, David A. Fox, Salahuddin Ahmed
Journal: Cellular and Molecular Immunology (2022)
A Genomically and Clinically Annotated Patient-Derived Xenograft Resource for Preclinical Research in Non–Small Cell Lung Cancer
Authors: Xing Yi Woo, Anuj Srivastava, Philip C. Mack, Joel H. Graber, Brian J. Sanderson, Michael W. Lloyd, Mandy Chen, Sergii Domanskyi, Regina Gandour-Edwards, Rebekah A. Tsai, James Keck, Mingshan Cheng, Margaret Bundy, Emily L. Jocoy, Jonathan W. Riess, William Holland, Stephen C. Grubb, James G. Peterson, Grace A. Stafford, Carolyn Paisie, Steven B. Neuhauser, R. Krishna Murthy Karuturi, Joshy George, Allen K. Simons, Margaret Chavaree, Clifford G. Tepper, Neal Goodwin, Susan D. Airhart, Primo N. Lara, Thomas H. Openshaw, Edison T. Liu, David R. Gandara, Carol J. Bult
Journal: Cancer Research (2022)

Abstract Patient-derived xenograft (PDX) models are an effective preclinical in vivo platform for testing the efficacy of novel drugs and drug combinations for cancer therapeutics. Here we describe a repository of 79 genomically and clinically annotated lung cancer PDXs available from The Jackson Laboratory that have been extensively characterized for histopathologic features, mutational profiles, gene expression, and copy-number aberrations. Most of the PDXs are models of non–small cell lung cancer (NSCLC), including 37 lung adenocarcinoma (LUAD) and 33 lung squamous cell carcinoma (LUSC) models. Other lung cancer models in the repository include four small cell carcinomas, two large cell neuroendocrine carcinomas, two adenosquamous carcinomas, and one pleomorphic carcinoma. Models with both de novo and acquired resistance to targeted therapies with tyrosine kinase inhibitors are available in the collection. The genomic profiles of the LUAD and LUSC PDX models are consistent with those observed in patient tumors from The Cancer Genome Atlas and previously characterized gene expression-based molecular subtypes. Clinically relevant mutations identified in the original patient tumors were confirmed in engrafted PDX tumors. Treatment studies performed in a subset of the models recapitulated the responses expected on the basis of the observed genomic profiles. These models therefore serve as a valuable preclinical platform for translational cancer research. Significance: Patient-derived xenografts of lung cancer retain key features observed in the originating patient tumors and show expected responses to treatment with standard-of-care agents, providing experimentally tractable and reproducible models for preclinical investigations.
A randomized trial of blood donor iron repletion on red cell quality for transfusion and donor cognition and well-being
Authors: Eldad A. Hod, Gary M. Brittenham, Zachary C. Bitan, Yona Feit, Jordan I. Gaelen, Francesca La Carpia, Luke A. Sandoval, Alice T. Zhou, Mark Soffing, Akiva Mintz, Joseph Schwartz, Connie Eng, Marta Scotto, Elise Caccappolo, Christian Habeck, Yaakov Stern, Donald J. McMahon, Debra A. Kessler, Beth H. Shaz, Richard O. Francis, Steven L. Spitalnik
Journal: Blood (2022)
Supraventricular Tachycardia Following Mitral Valve Surgery
Authors: Vincenzo Carbone, Giovanni Carbone, Antonio Cassese
Journal: JAMA Cardiology (2022)

A man in his mid-50s with a history of mitral valve repair presented to the emergency department with complaints of recent-onset palpitation. The QRS complexes displayed pairs of beats exhibiting complete right bundle branch block and QRS duration of 140 milliseconds followed by a third beat with normal configuration and QRS duration of 70 milliseconds. What would you do next?
Emergence of Delta and Omicron variants carrying resistance-associated mutations in immunocompromised patients undergoing sotrovimab treatment with long-term viral excretion
Authors: Cristina Andrés, Alejandra González-Sánchez, Moraima Jiménez, Ester Márquez-Algaba, Maria Piñana, Candela Fernández-Naval, Juliana Esperalba, Narcís Saubi, Josep Quer, Ariadna Rando-Segura, Marta Miarons, Maria Gema Codina, Isabel Ruiz-Camps, Tomàs Pumarola, Pau Abrisqueta, Andrés Antón
Journal: Clinical Microbiology and Infection (2022)
Leveraging Large-Scale Genetics of PTSD and Cardiovascular Disease to Demonstrate Robust Shared Risk and Improve Risk Prediction Accuracy
Authors: Antonia V. Seligowski, Burook Misganaw, Lucie A. Duffy, Kerry J. Ressler, Guia Guffanti
Journal: American Journal of Psychiatry (2022)

Objective: Individuals with posttraumatic stress disorder (PTSD) are significantly more likely to be diagnosed with cardiovascular disease (CVD) (e.g., myocardial infarction, stroke). The evidence for this link is so compelling that the National Institutes of Health convened a working group to determine gaps in the literature, including the need for large-scale genomic studies to identify shared genetic risk. The aim of the present study was to address some of these gaps by utilizing PTSD and CVD genome-wide association study (GWAS) summary statistics in a large biobank sample to determine the shared genetic risk of PTSD and CVD. Methods: A large health care biobank data set was used (N=36,412), combined with GWAS summary statistics from publicly available large-scale PTSD and CVD studies. Disease phenotypes (e.g., PTSD) were collected from electronic health records. De-identified genetic data from the biobank were genotyped using Illumina SNP array. Summary statistics data sets were processed with the following quality-control criteria: 1) SNP heritability h2 >0.05, 2) compute z-statistics (z=beta/SE or z=log(OR)/SE), 3) filter nonvariable SNPs (0<freq<1), and 4) filter SNPs with low number of samples. The multitrait analysis of GWAS (MTAG) approach was used to combine GWAS summary statistics. Results: Significant genetic correlations were found between PTSD and CVD (rG=0.24, SE=0.06), and Mendelian randomization analyses indicated a potential causal link from PTSD to hypertension (β=0.20, SE=0.04), but not the reverse. PTSD summary statistics significantly predicted PTSD diagnostic status (R2=0.27), and this was significantly improved by incorporating summary statistics from CVD and major depressive disorder (R2=1.30). Further, pathway enrichment analyses indicated that genetic variants involved in shared PTSD-CVD risk included those involved in postsynaptic structure, synapse organization, and interleukin-7-mediated signaling pathways. Conclusions: The results from this study suggest that PTSD and CVD may share genetic risk. Further, these results implicate PTSD as a risk factor leading to the development of hypertension and coronary artery disease. Additional research is needed to determine the clinical utility of these findings.